Platelet glycoprotein IIb/IIIa blockade with tirofiban: effect on aggregation caused by P256, an antibody to human IIb/IIIa receptors

Aims P256 is a divalent antibody which aggregates human platelets by intera ction with glycoprotein (GP) IIb/IIIa receptors. We investigated the effect of tirofiban, an antagonist of the GP IIb/IIIa receptor, on P256-mediated platelet aggregation. Methods Responses to agonists were measured turbidometrically at 37 degrees C in stirred citrated platelet-rich plasma front venous blood samples from healthy human volunteers. Inhibitory effects were determined by comparison with aggregation to the same concentration of agonist in a vehicle treated sample. Results Tirofiban inhibited a near maximally effective dose of P256 (10(-7) mol l(-1)) with an IC50 of 9.3 x 10(-8) mol l(-1). Tirofiban (10(-7) mol l (-1)) inhibited responses to arachidonic acid, U46619 and P256 similarly, w hereas aspirin (1.1x10(-4) mol l(-1)) inhibited arachidonic acid more effec tively than P256 (P<0.007 by ANOVA). Conclusions Tirofiban potently and selectively inhibits P256-stimulated agg regation of human platelets.